PROJECT SUMMARY Music therapy has become a standard palliative care service in many pediatric and adult hospitals. However, a majority of music therapy research has focused on the use of music to improve psychosocial dimensions of health, without considering biological dimensions. In addition, few studies have examined dose-response relationships. Cancer treatment is an inherently stressful experience, and a significant number of young children and parents (caregivers) experience persistent, interrelated emotional distress and poor quality of life. Many parents also experience traumatic stress symptoms because of their child's cancer diagnosis and treatment. Our previously tested Active Music Engagement (AME) intervention uses active music play to diminish stressful attributes of cancer treatment to help manage emotional/traumatic distress experienced by young children (ages 3-8) and parents and improve quality of life. A recent AME trial is examining psychosocial mechanisms of action responsible for change in child/parent outcomes. The current study expands on this work by examining AME's effects on several biomarkers to povide a more holistic understanding about how active music interventions work to mitigate cancer-related stress and its potential to improve immune function. The purposes of this two group, randomized controlled trial are to examine biological mechanisms of effect and dose-response relationships of AME on child/parent stress during the consolidation phase of Acute Lymphoblastic Leukemia (ALL) treatment. Specific aims are to: 1) establish whether AME lowers child and parent cortisol, 2) examine cortisol as a mediator of AME effects on child and parent outcomes, and 3) examine the dose-response relationship of AME on child and parent cortisol. Child/parent dyads (n=228) will be stratified (by age, site, ALL risk level) and randomized in blocks of four to AME or attention control. Each group will receive one 45-minute session during weekly clinic visits for the duration of ALL consolidation (4 weeks standard risk; 8 weeks high risk). Parents will complete measures at baseline and following the last study session. Child and parent salivary cortisol samples will be taken pre and post-session for the first 4 AME or attention control sessions. Child blood samples will be reserved from routine blood draws prior to sessions 1 and 4 (all participants) and session 8 (high risk participants). Linear mixed models will be used to estimate AME's effect on child and parent cortisol. Examining child and parent cortisol as mediators of AME effects on child and parent outcomes will be performed in an ANCOVA setting, fitting the appropriate mediation models using MPlus and then testing indirect effects using the percentile bootstrap approach to estimate the indirect effect. Graphical plots and non-linear repeated measures models will be used to examine the dose-response relationship of AME on child and parent cortisol. Findings will increase mechanistic understanding of the effects of active music interventions on multiple biomarkers and understanding of dose-response effects, with direct implications for the evidence-based use of music to improve health.